The ability to specifically and non-destructively incorporate inorganic structures into or through biological membranes is essential to realizing full bio-inorganic integration, such as arrayed on-chip patch-clamps, drug delivery, and biosensors. However, molecular delivery and interfaces to inorganic objects, such as patch-clamp pipettes, generally rely upon destructive formation of membrane holes and serendipitous adhesion, rather than selective penetration and attachment to the bilayer. In fact, materials greater than a few nanometers in size have not been shown to penetrate lipid bilayers without disrupting the continuity of the membrane. In this talk, I will discuss the development of nanofabricated probes that spontaneously insert into the hydrophobic membrane core by mimicking the hydrophobic banding of transmembrane proteins, forming a well-defined bio-inorganic lateral junction. These biomimetic ‘stealth’ probes consist of hydrophilic posts with 2-10 nm hydrophobic bands formed by molecular self-assembly, and are easily fabricated onto a variety of substrates including silicon wafers, nanoparticles, and atomic force microscope (AFM) tips.

 

By fabricating this architecture onto AFM probes, we have directly measured the penetration behavior and adhesion force of different molecular functionalities within the bilayer. It has been found that following insertion, the stealth probes remain anchored in the center of the bilayer, while purely hydrophilic probes have no preferred location. The strength of the stealth probe adhesion varies greatly between short and long chain alkane functionalizations, indicating that chain mobility, orientation, and hydrophobicity all contribute to molecular stability within the bilayer. In addition, the consequences of geometric factors such as band thickness and the presence of multiple bands on interface stability have been established. By selectively choosing the desired properties of the hydrophobic band, it will be shown that it is possible to tune the failure tension of the interface from values comparable to that of pristine lipid vesicles to only a fraction of the strength. Finally, the ability to transfer the stealth probe behavior to other platforms (e.g. nanoparticles for drug delivery) will be discussed.